Peripheral GABAA receptor-mediated signaling facilitates persistent inflammatory hypersensitivity.

摘要: Unlike in the central nervous system (CNS), adult peripheral (PNS), activation of GABAA receptors (GABAAR) is excitatory because relatively high concentration intracellular chloride these neurons. Indeed, exogenous GABA and muscimol, a GABAAR agonist, exacerbate acute inflammatory hypersensitivity rodents. However, it remains unclear whether endogenous play an important role persistent hypersensitivity. In this study, we thus investigated how affects pain by using complete Freund's adjuvant (CFA)-induced mouse model. We found that intraplantar (i.pl.) administration antagonists, picrotoxin, 1(S),9(R)-(-)-bicuculline methiodide significantly inhibited both spontaneous nociceptive (paw licking flinching) behavior mechanical CFA-injected mice at day 3 (D3), but not naive mice. Interestingly, CFA-induced was reversed anti-GABA antibody (anti-GABA, i.pl.). addition, RT-qPCR revealed glutamate decarboxylase Gad1 (GAD 67) Gad2 65) mRNA expression also upregulated ipsilateral hind paw D3. Finally, 5α-pregnan-3α-ol-20-one (3α,5α-THP), selective positive allosteric modulator GABAAR, produced dose-dependent manner. Taken together, our results indicate GABA, possibly inflamed tissue, potentiate hypersensitivity, suggesting they can be used as therapeutic target for alleviating pain.